Siddhartha Mukherjee: Have we lost the fire to tackle childhood cancers?

Siddhartha Mukherjee, MD, PhD, takes his audience on a tour of 60 years’ worth of successes in cancer. What does the future hold?

We’ve all heard the George Santayana quote, “Those who cannot remember the past are condemned to repeat it.” But there’s another way of thinking about the lessons that the past holds for the future: Those who do remember the past can recapture and harness earlier feelings of energy, urgency and possibility to overcome new problems, now and in the future.

In taking the audience on a tour through the last 60 years of advances in cancer biology, genomics and treatment, Mukherjee highlighted the central role pediatrics played as the starting point for the cancer successes we see today. How, he asked, did children come to play such a central role? What can we learn from the successes in the 1950s and ’60s, when pediatric cancer started to evolve from a death sentence to a treatable, even curable disease?

And how, he asked, can we recapture and harness the energy and urgency of that time today?

Back to the future

The most important piece of information we have about cancer, Mukherjee noted, came to light shortly after the first treatment success of the 1950s and ’60s: Cancer is primarily a genetic disease. “Today we take that idea a little bit for granted,” he explained, “but in the 1970s that was a radical idea.”

But how many genes need to be mutated in order to cause cancer? How common are those mutations? And do they overlap between cancers? These next questions, Mukherjee said, carried science through the next 20 years. The answers — which fueled the beginnings of cancer screening and underpinned cancer sequencing efforts like The Cancer Genome Atlas — exposed the complexity of cancer and the uniqueness of every cancer, and every cancer patient.

“Cancer biology does not ask us to do precision medicine as a sidenote,” he added. “Cancer medicine [instructs] us to do precision medicine as a fundamental basis. We don’t have an option.”

As Mukherjee noted, the first spectacular successes of cancer genomics — drugs such as Gleevec and Herceptin — revealed that the sum total of the cancer cell’s physiology is just as, if not more, important than the individual mutations that fuel it.

This is a much broader, and in some ways more daunting, view. It requires looking at the cancer cell as an organism, and accounting for everything that goes on within the cell and influences it from the outside.

“People have likened this to going into a network and shutting off its critical nodes,” Mukherjee says. “We began by shutting off one little switch, and the question is, Can we take multiple switches and shut them off, and would that finally bring the cancer cell to its end?”

The strategy of tracking and attacking a combination of targets, he noted, started in pediatrics. “The idea of shutting off multiple nodes was born in children’s cancers, and is being resurrected in the modern era with precision medicine. We’ve come full circle.”

Simple questions about cancer genes (How many genes are involved? How common are cancer mutations?) have revealed much about the disease’s complexity.

Recapturing a sense of urgency

Mukherjee noted that while this holistic view of cancer has fueled amazing innovations, including immunotherapies such as CAR T-cell engineering, he sees one last piece of the innovation puzzle missing today.

“If you look in the 1950s, there was a kind of desperation or urgency about the treatment of children’s cancers. [There] was a kind of fire that was lit that allowed an entire community to coalesce around the idea of cancer.

“The question I throw out quite broadly is, Have we lost some of that urgency?” he continued. “And if we have, we have to get it back. If we lose that fire, if we lose that urgency, we will begin to lose…the battle against cancer.”